Mengxu Zhu*, Avirup Ghosh and Hong Yan Pages 682 - 690 ( 9 )
Background: COVID-19 emerged in late 2019 and became a pandemic disease with severe mortality and morbidity. No specific remedy exists at present, but some drugs, such as Dexamethasone, have shown clinical benefits against the causative agent, the SARS-CoV-2 virus.Objective: To analyze the binding affinity between drugs and an SARS-CoV-2 protein through geometrical methods and to study the theoretical effectiveness of Dexamethasone as a potential treatment for COVID-19. Methods: The binding affinity of Dexamethasone to the target SARS-CoV-2 protein was compared with those of different inhibitors. Drug molecules were docked to the SARS-CoV-2 main protease, and the system was simulated by molecular dynamics, allowing alpha shape analysis to extract geometrical features, such as the matching rates of atoms, solid angles, and the distances between atoms at interfaces. Binding affinities between drugs and the main protease were assessed by these geometrical data and the free energy of binding. Results: The behaviour of Dexamethasone was similar to other inhibitors. The efficacy of Dexamethasone as a treatment may be due to it being a glucocorticoid and its properties as a potent inhibitor. Conclusion: This study revealed the mechanism of action of Dexamethasone and provided a geometrical method to distinguish among potential drugs for the treatment of COVID-19.
COVID-19, dexamethasone, inhibitor, molecular dynamics simulations, alpha shape analysis, geometrical features, matching rates.
Department of Electrical Engineering, City University of Hong Kong, Kowloon, Department of Electrical Engineering, City University of Hong Kong, Kowloon, Department of Electrical Engineering, City University of Hong Kong, Kowloon